In order to develop an effective vaccine against HIV, it will be necessary to develop new methods to prime T cell responses against HIV antigens. One way to prime such T cell responses is to create recombinant viral vectors that express HIV antigens. Recent results from a large scale clinical trial using recombinant adenovirus vectors as an experimental prophylactic HIV vaccine raise significant concerns that immune responses directed against the viral vector may have had a detrimental effect on vaccine efficacy, or may even have increased susceptibility to HIV infection. The purpose of the project described in this application is to develop new methods to prime HIV-specific T cell responses in a "vectorless" manner. Our proposed method will use various new nanoparticle technologies permit vaccine delivery by an intranasal route. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a vaccine that can prevent or reduce the severity of HIV infection in vaccinated subjects. The proposed vaccine will be composed of nucleic acids (RNA) and closely related compounds and will be administered by an intranasal route. If successful this vaccine will prime protective immunity in the absence of viral vectors or recombinant proteins, and without requiring needles or injection for delivery.